Sunday, 24 January 2010

"In this study all EBV-negative subjects (10 out of 10) who developed MS became EBV positive before MS onset. In contrast, only 36% (10 of the 28) controls subjects who were EBV-negative became EBV-positive with follow-up. Ascherio and colleagues conclude that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection."

Interpretation: This study is very important with regard to pinning down whether or not EBV causes MS. It ticks one of the criteria for causation; i.e. the correct temporal sequence. You need to get infected with EBV prior to MS onset.

I am often asked which oral would you prescribe? There is no simple answer to this question. The answer will depend on several factors some of which are still to emerge; to mention a few:

1. If and when these agents get licensed and the conditions of licensing; i.e. a first- or second-line indication.
2. The price and more importantly the cost-effectiveness of the agents; NICE will dictate the conditions of use in the UK.
3. Level of disease activity; inactive vs. active vs. highly-active disease.
4. Perceived long-term risk; infections and possible risk of malignancy.
5. Local infrastructure to start the orals.
6. Requirements and intensity of monitoring whilst on medication.
7. Fertility issues.
8. Previous use of other disease-modifying agents.
9. Underlying medical problems.
10. Etc, etc.

It is clear from the above that the decisions about which agent to use will be personalised and will depend largely on patient choice. It is important to ensure that patients have choice and that the choice is an informed one.

Oral cladribine reduced relapse rates and lowered the risk of sustained disability in patients with relapsing–remitting multiple sclerosis. Patients who were treated with cladribine had large reductions in lymphocyte counts and more infections, including one death from reactivation of tuberculosis.

European Medicines Agency recommends additional measures to better manage risk of progressive multifocal leukoencephalopathy (PML) with Tysabri. The risk of PML increases after two years, but benefits of Tysabri continue to outweigh risks for patients with highly active relapsing-remitting multiple sclerosis.

The European Medicines Agency has finalised a review of Tysabri (natalizumab) and the risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection caused by the JC virus. The Agency's Committee for Medicinal Products for Human Use (CHMP) has concluded that the risk of developing PML increases after two years of use of Tysabri although this risk remains low. However, the benefits of the medicine continue to outweigh its risks for patients with highly active relapsing-remitting multiple sclerosis, for whom there are few treatment options available.

Because it is important that PML is detected early, the Committee recommended that a number of measures be put in place to ensure that patients and doctors are fully aware of the risks of PML. These include:

* an update of the product information to add information about the increase in the risk of PML after two years of treatment and additional advice on how to manage patients who show signs of PML;
* forms to be signed by patients at the beginning of treatment with Tysabri, and again after two years of treatment, after in-depth discussions about the risk of PML with their doctor.

Measures to minimise the risk of PML were part of the initial marketing authorisation for Tysabri, issued in June 2006. Since then, they have been continuously updated and strengthened to increase awareness of the risk of PML.

The new measures are designed to complement the existing recommendations that patients, and their carers, partners and families should be made aware of the symptoms of PML and that patients should be closely monitored throughout treatment.

Notes

1. Tysabri, from Elan Pharma International Ltd, is used to treat relapsing-remitting multiple sclerosis in patients with high disease activity despite treatment with a beta-interferon or whose disease is severe and progressing rapidly.

2. More information about the review of Tysabri is available in a
question-and-answer document. http://www.ema.europa.eu/humandocs/PDFs/EPAR/tysabri/Tysabri_A20-29_Q&A.pdf

3. More information about Tysabri is available in the European Public Assessment Report: http://www.ema.europa.eu/humandocs/Humans/EPAR/tysabri/tysabri.htm

4. This press release, together with other information on the work of the European Medicines Agency, can be found on the Agency's website: www.ema.europa.eu

PML Risk Infographic

Holistic Management of MS ver. 7.0

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